Multi-functional DNA-conjugated nanohydrogels for aptamer-directed breast cancer cell targeting

The development of new conjugation chemistry involving DNA and nanoparticles as well as nanoparticle-based platforms for aptamer-directed cancer-cell targeting is important for improved targeted therapy and imaging. Herein, a dual stimuli-responsive DNA-conjugated nanohydrogel was prepared by direct copolymerization of methacrylic acid and acrydite-DNA using a disulfide bond-containing crosslinker. DNA-conjugated nanohydrogels possess a drug-loading capacity of >30% and good pH/redox responsivity. Furthermore, various functional nucleic acids, such as aptamers, can easily be loaded on the surface of nanohydrogels by hybridization. After the loading of doxorubicin (Dox) and MUC1 aptamers, the obtained aptamer-functionalized nanohydrogels were used for MCF-7 human breast cancer-cell targeting. We observed that the aptamer-functionalized nanohydrogels were not only selectively taken up by MCF-7 cancer cells but also exhibited enhanced cytotoxicity in MCF-7 cancer cells compared with MCF-10A normal human breast epithelial cells. This combined copolymerization-hybridization method for the preparation of aptamer-functionalized nanohydrogels exhibits promising potential for targeted therapy and imaging applications.